The broad, long-term objectives of this research are: 1) to define the role of pathogen-related oral spirochetes (PROS) in the etiology and pathogenesis of periodontal diseases; and 2) to utilize that information to improve methods for diagnosis, prevention and treatment. Specific Aims for research are derived from collaborative studies in our laboratories that led to the discovery that dental plaque and diseased gingiva from patients with periodontitis contain spirochetes that display significant homology with antigens previously thought to be unique to the well-recognized pathogen, Treponema pallidum. T. pallidum monoclonal antibodies (mAbs) used to identify these spirochetes react with subspecies of T. pallidum but not with cultivable treponemes, including cultivable oral treponemes. We have obtained evidence that PROS, like T. pallidum, are invasive and can pass through a tissue barrier. The research in this proposal is intended to accomplish the following: 1) Define the prevalence of PROS in patients with periodontitis. This research is intended to validate the relationship of PROS with acute and chronic forms of periodontitis by examining dental plaque for PROS with pathogen-restricted mAbs; 2) Examine serum from patients with periodontitis for antibodies to pathogen-restricted antigens of T. pallidum. This research is intended to confirm the relationship of PROS to known pathogenic treponemes by demonstrating the presence of antibodies to T. pallidum-restricted antigens in sera of patients with periodontitis using immunoblots and other serologic assays; 3) Establish conditions for the propagation of PROS in vitro and/or in vivo. This research is intended to find conditions under which PROS will replicate so that isolates can be maintain and studied; 4) Characterize PROS isolates in terms of antigenic, phenotypic and DNA homology to known cultivable and pathogenic spirochetes. This research is intended to describe the taxonomic relationship of PROS with other spirochetes and to estimate its heterogeneity in nature; and 5) Study potential mechanisms of PROS pathogenesis. These studies will identify processes that may contribute to disease. In summary, these studies will lead to the identification and characterization of a new oral spirochete, one that may play an important role in some forms of periodontal disease.